EZH1 has more to offer than gene repression

Tue, 05/03/2016 - 15:28

EZH1 is part of the Polycomb-group family of proteins, which are responsible for remodeling chromatin in genes and modulating epigenetic silencing during development. Specifically, EZHI is a component of PRC2, or polycomb repressive complex-2. PRC2 interacts and modifies the histone “H3”, and is critical in maintaining gene repression. EZH1 has the ability to mono-, di- and tri-methylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. EZH1 is also implicated in the maintenance of embryonic stem cells, including their differentiation and renewal.

Margueron et al took a closer look at the mammalian homologs of EZH1 and EZH2 in order to learn more about their similarities and differences during development (1). They found that while both Ez proteins form PRC2 complexes, they carry out different repressive roles. Ultimately, both protein complexes are efficient at catalyzing H3K27me2/3, however the effect of global knockdown of H3K27me2/3 is only accomplished by EZH2. Both EZH1 and EZH2 antibodies were used to first establish the formation of a PRC2 complex, and then to examine the effect on downstream H3K27me2/3 levels, also using an H3K27me2/3 antibody. Their results may reflect more functionalization of PcG proteins during evolution.

In a fairly recent Molecular Cell preview article, Mousavi et al shared their finding that EZH1 exhibits a novel gene activation function alongside its longtime established role as a transcriptional repressor (2). Through an extensive study of EZH1 and EZH2 in myoblasts, their group used genome mapping to discover that out of the 2,000-3,000 genes that EZH1 was associated with, only 13% were of the H3k27me3. To further elucidate the role of EZH1 in differentiation, Mousavi’s group knocked down EZH1 expression in myoblasts and found that the catalytic domain of EZH1 is required for the premature activation of key proteins involved in myoblast differentiation. Similar studies were performed by Yoo et al using both H3K27me3 and EZH2 antibodies to show that in the absence of EZH1 and EZH2, differentiated mammary epithelia did not form (3). This is another example of the activation function of the Ez proteins in a different tissue. An additional study from Liu et al used EZH1 and EZH2 antibodies alongside RNA interference, qtPCR and ChIP analysis to elucidate the novel role of EZH1 in dendritic cell maturation. Their research revealed that not only is EZH1 the most upregulated histone methyltransferase during DC maturation, but that silencing EZH1’s activity in turn activated a long line of innate immune response factors.